Skip to main content
SpringerLink
Log in

NAFLD in Children: Implication for the Future

  • Chapter
  • First Online:
Non-Alcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver pathology, ranging from simple hepatic steatosis to more advanced forms of liver damage, up to cirrhosis. It has been described an important increase in the prevalence of NAFLD, likely related to the dramatic rise in the incidence of obesity during the past three decades. Despite an increase in public awareness, overweight/obesity and related conditions, such as NAFLD, remain underdiagnosed and underestimated.

The literature of last decades contains several advances not only to further elucidate the genetic/pathogenetic mechanisms that lead to pediatric NAFLD but also allows to make many steps forward both on the diagnosis and therapy of children and adolescents with NAFLD.

The aim of this chapter is to provide an overview of the actual knowledge in the field of pediatric NAFLD, with particular attention to the novel discoveries in terms of diagnosis and therapy and its future implications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Nobili V, Svegliati-Baroni G, Alisi A, Miele L, Valenti L, Vajro P. A 360-degree overview of paediatric NAFLD: recent insights. J Hepatol. 2013;58:1218–29.

    Article  PubMed  Google Scholar 

  2. Vajro P, Lenta S, Socha P, et al. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2012;54:700–13.

    Article  PubMed  Google Scholar 

  3. Yki-Jarvinen H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol. 2014;2:901–10.

    Article  CAS  PubMed  Google Scholar 

  4. Hadžić N, Baumann U, McKiernan P, McLin V, Nobili V. Long-term challenges and perspectives of pre-adolescent liver disease. Lancet Gastroenterol Hepatol. 2017;2(6):435–45.

    Article  PubMed  Google Scholar 

  5. Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut. 2009;58:1538–44.

    Article  CAS  PubMed  Google Scholar 

  6. Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43(8):617–49.

    Article  PubMed  Google Scholar 

  7. Mann JP, Raponi M, Nobili V. Clinical implications of understanding the association between oxidative stress and pediatric NAFLD. Expert Rev Gastroenterol Hepatol. 2017;11(4):371–82.

    Article  CAS  PubMed  Google Scholar 

  8. Doulberis M, Kotronis G, Gialamprinou D, et al. Non-alcoholic fatty liver disease: an update with special focus on the role of gut microbiota. Metabolism. 2017;71:182–97.

    Article  CAS  PubMed  Google Scholar 

  9. Del Chierico F, Nobili V, Vernocchi P, et al. Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach. Hepatology. 2017;65(2):451–64.

    Article  PubMed  CAS  Google Scholar 

  10. Schwimmer JB, Behling C, Newbury R, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42:641–8.

    Article  PubMed  Google Scholar 

  11. Manco M, Marcellini M, Devito R, Comparcola D, Sartorelli MR, Nobili V. Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes. 2008;32:381–7.

    Article  CAS  Google Scholar 

  12. Jazwinski AB, Thompson AJ, Clark PJ, Naggie S, Tillmann HL, Patel K. Elevated serum CK18 levels in chronic hepatitis C patients are associated with advanced fibrosis but not steatosis. J Viral Hepat. 2012;19(4):278–82.

    Article  CAS  PubMed  Google Scholar 

  13. Vos MB, et al. Cytokeratin 18, a marker of cell death, is increased in children with suspected nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2008;47(4):481–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bateman AC, Hübscher SG. Cytokeratin expression as an aid to diagnosis in medical liver biopsies. Histopathology. 2010;56(4):415–25.

    Article  PubMed  Google Scholar 

  15. Walenbergh SM, et al. Plasma cathepsin D levels: a novel tool to predict pediatric hepatic inflammation. Am J Gastroenterol. 2015;110(3):462–70.

    Article  CAS  PubMed  Google Scholar 

  16. Pingitore P, Romeo S. The role of PNPLA3 in health and disease. Biochim Biophys Acta. 2019;1864(6):900–6. pii: S1388-1981(18)30145-8

    Article  CAS  Google Scholar 

  17. Mangge H, Baumgartner BG, Zelzer S, Pruller F, Schnedl WJ, Reininghaus EZ, Haybaeck J, Lackner C, Stauber R, Aigner E, et al. Patatin-like phospholipase 3 (rs738409) gene polymorphism is associated with increased liver enzymes in obese adolescents and metabolic syndrome in all ages. Aliment Pharmacol Ther. 2015;42:99–105.

    Article  CAS  PubMed  Google Scholar 

  18. Carpino G, Pastori D, Baratta F, et al. PNPLA3 variant and portal/periportal histological pattern in patients with biopsy-proven non-alcoholic fatty liver disease: a possible role for oxidative stress. Sci Rep. 2017;7(1):15756.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Nobili V, Donati B, Panera N, et al. A 4-polymorphism risk score predicts steatohepatitis in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2014;58(5):632–6.

    Article  CAS  PubMed  Google Scholar 

  20. Wieckowska A, McCullough AJ, Feldstein AE. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology. 2007;46:582–9.

    Article  CAS  PubMed  Google Scholar 

  21. Nobili V, Monti L, Alisi A, Lo Zupone C, Pietrobattista A, Tomà P. Transient elastography for assessment of fibrosis in paediatric liver disease. Pediatr Radiol. 2011;41(10):1232–8.

    Article  PubMed  Google Scholar 

  22. Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J, Zeuzem S, Herrmann E. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134:960–74.

    Article  PubMed  Google Scholar 

  23. Garcovich M, et al. Liver stiffness in pediatric patients with fatty liver disease: diagnostic accuracy and reproducibility of shear-wave elastography. Radiology. 2016;13:161002.

    Google Scholar 

  24. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, Friedman SL, Diago M, Romero-Gomez M. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367–78.e5.

    Article  PubMed  Google Scholar 

  25. Africa JA, Newton KP, Schwimmer JB. Lifestyle interventions including nutrition, exercise, and supplements for nonalcoholic fatty liver disease in children. Dig Dis Sci. 2016;61:1375–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Softic S, Cohen DE, Kahn CR. Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Dig Dis Sci. 2016;61(5):1282–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lavine JE, Schwimmer JB, Van Natta ML, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011;305:1659–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Della Corte C, Carpino G, De Vito R, De Stefanis C, Alisi A, Cianfarani S, Overi D, Mosca A, Stronati L, Cucchiara S, Raponi M, Gaudio E, Byrne CD, Nobili V. Docosahexanoic acid plus vitamin D treatment improves features of NAFLD in children with serum vitamin D deficiency: results from a single centre trial. PLoS One. 2016;11(12):e0168216.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Miele L, Marrone G, Lauritano C, et al. Gut-liver axis and microbiota in NAFLD: insight pathophysiology for novel therapeutic target. Curr Pharm Des. 2013;19:5314–24.

    Article  CAS  PubMed  Google Scholar 

  30. Alisi A, Bedogni G, Baviera G, Giorgio V, Porro E, Paris C, Giammaria P, Reali L, Anania F, Nobili V. Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2014;39(11):1276–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Molinaro A, Wahlström A, Marschall HU. Role of bile acids in metabolic control. Trends Endocrinol Metab. 2018;29(1):31–41. pii: S1043-2760(17)30151-0.

    Article  CAS  PubMed  Google Scholar 

  32. Nobili V, Alisi A, Mosca A, et al. Hepatic farnesoid X receptor protein level and circulating fibroblast growth factor 19 concentration in children with NAFLD. Liver Int. 2018;38(2):342–9.

    Article  CAS  PubMed  Google Scholar 

  33. Sepe V, Distrutti E, Fiorucci S, Zampella A. Farnesoid X receptor modulators 2014-present: a patent review. Expert Opin Ther Pat. 2018;28(5):351–64.

    Article  CAS  PubMed  Google Scholar 

  34. Steinacher D, Claudel T, Trauner M. Therapeutic mechanisms of bile acids and nor-ursodeoxycholic acid in non-alcoholic fatty liver disease. Dig Dis. 2017;35(3):282–7.

    Article  PubMed  Google Scholar 

  35. Neuschwander-Tetri BA, Loomba R, Sanyal AJ, NASH Clinical Research Network. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385(9972):956–65.

    Article  CAS  PubMed  Google Scholar 

  36. Eguchi Y, Kitajima Y, Hyogo H, Japan Study Group for NAFLD (JSG-NAFLD). Pilot study of liraglutide effects in non-alcoholic steatohepatitis and non-alcoholic fatty liver disease with glucose intolerance in Japanese patients (LEAN-J). Hepatol Res. 2015;45(3):269–78.

    Article  CAS  PubMed  Google Scholar 

  37. Nobili V, Della Corte C, Liccardo D, Mosca A, Caccamo R, Morino GS, Alterio A, De Peppo F. Obalon intragastric balloon in the treatment of paediatric obesity: a pilot study. Pediatr Obes. 2015;10(5):e1–4.

    Article  CAS  PubMed  Google Scholar 

  38. Nobili V, Vajro P, Dezsofi A, et al. Indications and limitations of bariatric intervention in severely obese children and adolescents with and without nonalcoholic steatohepatitis: ESPGHAN Hepatology Committee position statement. J Pediatr Gastroenterol Nutr. 2015;60:550–61.

    Article  PubMed  Google Scholar 

  39. Manco M, Mosca A, De Peppo F, et al. The benefit of sleeve gastrectomy in obese adolescents on nonalcoholic steatohepatitis and hepatic fibrosis. J Pediatr. 2017;180:31–37.e2.

    Article  PubMed  Google Scholar 

  40. Albaugh VL, Abumrad NN. Surgical treatment of obesity. F1000Res. 2018;7:F1000 Faculty Rev-617. https://doi.org/10.12688/f1000research.13515.1. eCollection 2018.

  41. Fiorucci S, Biagioli M, Distrutti E. Future trends in the treatment of non-alcoholic steatohepatitis. Pharmacol Res. 2018;134:289–98.

    Article  CAS  PubMed  Google Scholar 

  42. Alkhouri N, Hanouneh IA, Zein NN, et al. Liver transplantation for nonalcoholic steatohepatitis in young patients. Transpl Int. 2016;29(4):418–24.

    Article  CAS  PubMed  Google Scholar 

  43. Pais R, Barritt AS, Calmus Y, et al. NAFLD and liver transplantation: current burden and expected challenges. J Hepatol. 2016;65(6):1245–57.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hepatology, Gastroenterology and Nutrition Unit, “Bambino Gesù” Children’s Hospital, IRCCS, Rome, Italy

    Claudia Della Corte, Antonella Mosca, Andrea Pietrobattista, Maria Sole Basso & Valerio Nobili

  2. Pediatric Department, University La Sapienza Rome, Rome, Italy

    Valerio Nobili

Authors
  1. Claudia Della Corte
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonella Mosca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Pietrobattista
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Sole Basso
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Valerio Nobili
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudia Della Corte .

Editor information

Editors and Affiliations

  1. Department of Medical Sciences, Division of Gastroentrology and Hepatology, University of Turin, Turin, Italy

    Elisabetta Bugianesi

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Della Corte, C., Mosca, A., Pietrobattista, A., Basso, M.S., Nobili, V. (2020). NAFLD in Children: Implication for the Future. In: Bugianesi, E. (eds) Non-Alcoholic Fatty Liver Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-95828-6_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-95828-6_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-95827-9

  • Online ISBN: 978-3-319-95828-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation